During the next fiscal year we will complete a series of experiments on normal hemopoietic stem cell renewal by using in vivo techniques, whereby the stem cells are grown in two regions of the mouse spleen - one region is not irradiated while the other is irradiated at 4000 rads. These experiments will show clearly that stem cell growth depends on short range cell-cell contacts and cannot be attributed to microdiffusing or freely circulating growth factors. With the funds available we will start a similar series of experiments to check whether the same mechanism holds also for virus infected Friend leukemic stem cells. These experiments, hopefully will add evidence to the ideas that leukemic stem cells are not autonomously growing tumoral cells but, rather, intrinsically normal stem cells under the influence of a virally modified microenvironment. BIBLIOGRAPHIC REFERENCES: Rife, L.L., Sizemore, D. and Matioli, G. Induction of differentiation instabilities in Friend erythroleukemia. J. Reticuloendoth. Soc. 18: 97, 1975. Matioli. G. Consideration of some functional properties of the hemopoietic sources. Math. Biosciences. 28: 373, 1976.